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Role of 5-hydroxymethylcytosine level in diagnosis and prognosis prediction of intrahepatic cholangiocarcinoma

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Tumor Biology

Abstract

The loss of 5-hydroxymethylcytosine (5-hmC) has been identified as an epigenetic hallmark in several malignancies. However, its role in intrahepatic cholangiocarcinoma (ICC) is still unknown. Our study aims to investigate the level of 5-hmC in diagnosis and prognosis prediction of ICC. The 5-hmC levels were detected using dot blot, tissue microarray technique and immunohistochemical method, and the correlation between 5-hmC level and ICC clinicopathological parameters was analysed. Compared with matched liver tissues, most of ICC tissues presented with the loss of 5-hmC. Furthermore, the subgroups of cirrhotic and poor differentiation tissues showed the lowest level of 5-hmC. We found that 5-hmC level in non-elevated ICC patients was significantly related to lymph node metastasis and TNM stage and not related to vessel invasion, sex, age, HBV, cirrhosis or degree of differentiation. ICC patients with high TNM stage (stages III and IV) and lymph node metastases had significantly lower 5-hmC level than those with low TNM stage (stages I and II) and no lymph node metastases. Further analysis showed that low 5-hmC level is significantly correlated with worse overall survival (OS) and disease-free survival (DFS). Importantly, multivariate analysis indicated that 5-hmC level, tumour diameter, lymphatic metastasis and tumour differentiation could be used as independent prognostic factors for ICC. The loss of 5-hmC is implicated in the progression of ICC. Our results can contribute to the diagnostic ability and postoperative surveillance of ICC patients.

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Acknowledgments

This study was supported by the National Key Sci-Tech Project (2012ZX10002011-002), the National Natural Science Foundation of China (81472840, 81172023, 81071741 and 81030038) and the Shanghai Municipal Natural Science Foundation (14ZR1405800, 11ZR1428300, 114119a5000).

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Authors and Affiliations

  1. Liver Cancer Institute and Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China

    Zhao-Ru Dong, Chi Zhang, Jia-bin Cai, Peng-Fei Zhang, Guo-Ming Shi, Dong-mei Gao, Hui-Chuan Sun, Shuang-Jian Qiu, Jian Zhou, Ai-Wu Ke & Jia Fan

  2. Cancer Center, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200031, China

    Jian Zhou & Jia Fan

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  1. Zhao-Ru Dong
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  2. Chi Zhang
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  3. Jia-bin Cai
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  9. Jian Zhou
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  11. Jia Fan
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Correspondence to Ai-Wu Ke or Jia Fan.

Additional information

Zhao-Ru Dong, Chi Zhang, Jia-bin Cai and Peng-Fei Zhang contributed equally to this work.

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Dong, ZR., Zhang, C., Cai, Jb. et al. Role of 5-hydroxymethylcytosine level in diagnosis and prognosis prediction of intrahepatic cholangiocarcinoma. Tumor Biol. 36, 2763–2771 (2015). https://doi.org/10.1007/s13277-014-2900-2

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  • DOI: https://doi.org/10.1007/s13277-014-2900-2

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